The objective of this research program is to contribute to an understanding of the molecular basis of the biological activities of membrane-bound proteins. We have chosen to examine in detail one electron transport sequence of liver endoplasmic reticulum, the NADH and oxygen dependent stearyl-CoA desaturase, which involves an enzyme sequence of cytochrome b5 reductase, cytochrome b5 and stearyl-CoA desaturase. By limiting the scope of the experimental systems, we can hope to accomplish a very detailed description of the structures of the individual enzyme, the mechanism of electron transfer reactions, the segments of the tertiary structure of the proteins that participate in interactions with lipid bilayers, the mobility and flexibility of each enzyme in lipid bilayers, and the consequences of the insertion of these proteins in a phospholipid bilayer to achieve optimal orientation for catalytically productive interactions between the components of a sequential electron transport pathway. This will require not only application of the methodology of protein chemistry to the difficult analysis of nonpolar peptide primary, secondary and tertiary structure, but also an increased use of a variety of physical, chemical and immunologic methods, e.g., nuclear magnetic resonance, fluorescence energy transfer, and bifunctional cross-linking reagents, to achieve our goal of defining the protein-protein and protein-lipid interactions in one membrane bound enzyme system. In addition to such basic information concerning membrane structure and function, the system chosen has direct implications for two health related problems: 1) Since cytochrome b5 can also function as an electron donor for microsomal mixed function oxidation it may be significant in liver detoxication reactions and in the conversion of certain drugs to carcinogens; and 2) the fact that fatty acids have been widely implicated in hypercholesterolemia, a constant finding in atherosclerosis, emphasizes the need for the information on one mechanism by which the human might regulate fatty acid desaturation as part of a comprehensive evaluation of significant factors involved in this circulatory disease.